Is Brain Mapping Ready for Big Science?

The BAM project will be an expensive undertaking. Will it be worth the cost?

The Brain Activity Map Project is aimed at reconstructing the full record of neural activity across complete neural circuits, with the goal of understanding fundamental and pathological brain processes. [V. Yakobchuk/Fotolia.com]

President Barack Obama’s public-private initiative to create an activity map of the human brain will cost more than $3 billion, projections say, or $300 million annually for 10 years. The project has multiple private and public institutions lined up to participate, including the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation. All parties hope that the initiative will move brain science forward with the same kind of money and focused effort that drove the Genome Project.

“Every dollar we invested to map the human genome returned $140 to our economy—every dollar,” the president commented. “Today our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs, devising new materials to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation.”

George M. Church, Ph.D., professor of genetics at Harvard Medical School and director of PersonalGenomes.org, said he was helping to plan the Brain Activity Map project.

“If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck,” he commented in the New York Times.

BAM

The proposal for the project came from six scientists, among them Dr. Church, who said in the journal Neuron, “We propose launching a large-scale, international public effort, the Brain Activity Map project (BAM), aimed at reconstructing the full record of neural activity across complete neural circuits. This technological challenge could prove to be an invaluable step toward understanding fundamental and pathological brain processes.”

The collective idea for the initiative was generated at a meeting of neuroscientists and nanoscientists convened in September 2011 at the Kavli Royal Society International, U.K., organized by Tom Kalil, deputy director for policy at the White House’s Office of Science and Technology Policy (OSTP), and Miyoung Chun, Ph.D., vice president of science programs at the Kavli Foundation in Oxnard, California.

The Kavli institute has founded institutes for brain science at UC San Diego, Yale, and the Norwegian University of Science and Technology.

Meeting attendees articulated the issues the BAM will address in its report, mentioning “our persistent ignorance of the brain’s micro-circuitry—the minute and multitudinous connections contained within,” and citing the great brain scientist Ramon y Cajal’s 1923 quote that refers to the interconnected, intermixed, and dynamical network of different cell types as “impenetrable jungles where many investigators have lost themselves.” “Another equally fundamental shortcoming,” they noted, “is our inability to monitor network interactions and coordinated brain activities densely, and to do so simultaneously across extended regions of the brain, and with sufficient temporal and spatial resolution.”

And most scientists, whether proponents or opponents of the big science approach to brain mapping, agree that its biggest challenge is the need to develop novel tools to study the brain.

Revolutionary New Tools Needed

Partha Mitra, Ph.D., a theoretical physicist and currently Crick-Clay professor of biomathematics at Cold Spring Harbor Laboratory, says that current methods to visualize living or dead brains provide only glimpses of small portions of the full spatial extent of neurons in the human brain, or pictures of thin sections of brain, with pieces of the neurons in them. “No one has yet seen, under the microscope or in digital reconstruction, a complete human brain neuron that sends projections to distant parts of the brain. To do that at the whole-brain scale would be like seeing a new continent or planet.” Dr. Mitra’s research currently combines experimental, theoretical, and informatics approaches to gain an understanding of how brains work.

Dr. Chun has been developing the project since the beginning and has described herself as the “glue” holding the diverse stakeholders together. She told Nature that “there’s clearly an issue with tool development—and not just amending current, existing tools, although that will be important in the initial stages. In the long run, one of the very important points would be to come up with revolutionary new tools that will measure brain activity in a completely different way than what we know now.”

And project proponents say the only way to tackle some thus far tricky intractable human diseases, like Alzheimer’s and Parkinson’s disease, is with a huge program. “We are right on the edge of finding out really vital information about the brain,” says Brown University neuroscientist John Donoghue, Ph.D., who was part of the project team. “There are questions we can now answer that can only be tackled as a collaborative project,” not by individual labs.

In Dr. Donaghue's view, the problem is that the people developing novel technologies and the neuroscience community don’t communicate effectively. Biologists don't know enough about the tools already out there, and the materials scientists aren't getting feedback from them on ways to make their tools more useful.

Economic Incentives

And there’s no denying the economic incentives the project provides. “What motivates people to pursue these big projects is not the belief that they will solve problems,” says Michael Eisen, Ph.D., a biologist at the University of California, Berkeley. “It’s the belief that this is the way to get money.”

John Mazziotta, M.D., Ph.D., UCLA’s department of neurology chair and director of its Brain Mapping Center, says, “This initiative is more comprehensive than anything I’ve ever seen medicine and neuroscience. This effort will be both the stimulus and the challenge to work and collaborate in ways we haven’t done before, but always have wanted to.”

UCLA will likely benefit handsomely from the initiative as it says it is “well-positioned” to play a significant role in the effort and to capture funding that will support such an initiative, owing to the existence Ahmanson-Lovelace Brain Mapping Center and its “excellence” in nanoscience and nanotechnology.

Dr. Church is also in favor of spreading the funding for the project around. In an interview with Harvard Medical School News last month, he said, “The Genome Project didn’t adequately embrace small science. I think enabling small labs to do amazing things might be more powerful than having a juggernaut of a large lab, or worse yet, a race among a few large labs.”

A report from the Battelle Technology Partnership says that, between 1988 and 2010, federal investment in genomic research generated an economic impact of $796 billion, “impressive” considering that Human Genome Project (HGP) spending between 1990–2003 amounted to $3.8 billion and an ROI of 141:1.

Apart from job creation and ROI, if this massive initiative provides new treatment targets for intractable human neurological and psychiatric disorders, it will have been worth the investment.